Toll-Like Receptor 4 Mediates Acute Lung Injury Induced by High Mobility Group Box-1

During cardiopulmonary bypass (CPB), pulmonary ischemia/reperfusion (I/R) injury can cause acute lung injury (ALI). Our previous research confirmed that abnormal high-mobility group box 1 (HMGB1) release after CPB was closely related to ALI. However, the mechanism underlying the HMGB1-mediated induction of ALI after CPB is unclear. Our previous study found that HMGB1 binds Toll-like receptor 4 (TLR4), leading to lung injury, but direct evidence of a role for these proteins in the mechanism of CPB-induced lung injury has not been shown. We examined the effects of inhibiting HMGB1 or reducing TLR4 expression on CPB-induced lung injury in rats administered anti-HMBG1 antibody or TLR4 short-hairpin RNA (shTLR4), respectively. In these rat lungs, we studied the histologic changes and levels of interleukin- (IL-) 1β, tumour necrosis factor- (TNF-) α, HMGB1, and TLR4 after CPB. After CPB, the lung tissues from untreated rats showed histologic features of injury and significantly elevated levels of IL-1β, TNF-α, HMGB1, and TLR4. Treatment with anti-HMGB1 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1β, TNF-α, HMGB1, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB. Treatment with shTLR4 attenuated the CPB-induced morphological inflammatory response and protein levels of IL-1β, TNF-α, and TLR4 in the lung tissues and eventually alleviated the ALI after CPB, but could not alleviate the HMGB1 protein levels induced by CPB. In summary, the present study demonstrated that the HMGB1/TLR4 pathway mediated the development of ALI induced by CPB.

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The high-mobility group protein B1–Toll-like receptor 4 pathway contributes to the acute lung injury induced by bilateral nephrectomy

Kidney International ◽

10.1038/ki.2014.62 ◽

2014 ◽

Vol 86 (2) ◽

pp. 316-326 ◽

Cited By ~ 38

Author(s):

Kent Doi ◽

Tomoko Ishizu ◽

Maki Tsukamoto-Sumida ◽

Takahiro Hiruma ◽

Tetsushi Yamashita ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

High Mobility ◽

High Mobility Group ◽

Toll Like Receptor ◽

Bilateral Nephrectomy ◽

High Mobility Group Protein ◽

Toll Like Receptor 4 ◽

Group Protein

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Chelidonine Attenuates Sepsis-Induced Acute Lung Injury via Suppressing Toll-like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-॔B Signaling Pathway in Newborn Mice

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:120-126 ◽

2020 ◽

Vol 19 (1) ◽

pp. 120-126

Author(s):

Ayinuerguli Adili ◽

Adilijiang Kari ◽

Chuanlong Song ◽

Abulaiti Abuduhaer

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Nuclear Factor Kappa B ◽

Myeloid Differentiation ◽

Nuclear Factor ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Inflammatory Infiltration ◽

Newborn Mice ◽

Myeloid Differentiation Factor

We have examined the mechanism underlying amelioration of sepsis-induced acute lung injury by chelidonine in newborn mice. To this end, a sepsis model was established using cecal ligation and puncture in newborn mice. The sepsis-induced acute lung injury was associated with an increased inflammatory infiltration and pulmonary congestion, as well as abnormal alveolar morphology. The lung injury-associated increased tumor necrosis factor-α and interleukin-1β in bronchoalveolar lavage fluid and lung, the markers of inflammatory infiltration and pulmonary congestion, diminished by chelidonine treatment. Chelidonine administration also downregulated protein levels of toll-like receptor 4, myeloid differentiation factor 88, phosphorylated nuclear factor-kappa B, and nuclear factor-kappa B that are elevated in response to sepsis. In conclusion, chelidonine provides a potential therapeutic strategy for newborn mice with acute lung injury.

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Juglone Attenuates Sepsis-Induced Acute Lung Injury via Suppression of the TLR4/Nf-κb Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.18:201-206 ◽

2020 ◽

Vol 18 (2) ◽

pp. 201-206

Author(s):

Qiu Nan ◽

Xu Xinmei ◽

He Yingying ◽

Fan Chengfen

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Nuclear Factor Kappa B ◽

Cecal Ligation ◽

Myeloperoxidase Activity ◽

Nuclear Factor ◽

Cecal Ligation And Puncture ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Nuclear Factor Kappa

Sepsis, with high mortality, induces deleterious organ dysfunction and acute lung injury. Natural compounds show protective effect against sepsis-induced acute lung injury. Juglone, a natural naphthoquinone, demonstrates pharmacological actions as a pro-apoptotic substrate in tumor treatment and anti-inflammation substrate in organ injury. In this study, the influence of juglone on sepsis-induced acute lung injury was investigated. First, a septic mice model was established via cecal ligation and puncture, and then verified via histopathological analysis of lung tissues, the wet/dry mass ratio and myeloperoxidase activity was determined. Cecal ligation and puncture could induce acute lung injury in septic mice, as demonstrated by alveolar damage and increase of wet/dry mass ratio and myeloperoxidase activity. However, intragastric administration juglone attenuated cecal ligation and puncture-induced acute lung injury. Secondly, cecal ligation and puncture-induced increase of inflammatory cells in bronchoalveolar lavage fluid was also alleviated by the administration of juglone. Similarly, the protective effect of juglone against cecal ligation and puncture-induced acute lung injury was accompanied by a reduction of pro-inflammatory factor secretion in bronchoalveolar lavage fluid and lung tissues. Cecal ligation and puncture could activate toll-like receptor 4/nuclear factor-kappa B signaling pathway, and administration of juglone suppressed toll-like receptor 4/nuclear factor-kappa B activation. In conclusion, juglone attenuated cecal ligation and puncture-induced lung damage and inflammatory response through inactivation of toll-like receptor 4/nuclear factor-kappa B, suggesting a potential therapeutic strategy in the treatment of sepsis-induced acute lung injury.

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High-Mobility Group Box 1 (HMGB1) and Autophagy in Acute Lung Injury (ALI): A Review

Medical Science Monitor ◽

10.12659/msm.912867 ◽

2019 ◽

Vol 25 ◽

pp. 1828-1837 ◽

Cited By ~ 17

Author(s):

Lihua Qu ◽

Chao Chen ◽

YangYe Chen ◽

Yi Li ◽

Fang Tang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

High Mobility ◽

High Mobility Group

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Salidroside Protects Against Influenza A Virus-Induced Acute Lung Injury in Mice

Dose-Response ◽

10.1177/15593258211011335 ◽

2021 ◽

Vol 19 (2) ◽

pp. 155932582110113

Author(s):

Rufeng Lu ◽

Yueguo Wu ◽

Honggang Guo ◽

Zhuoyi Zhang ◽

Yuzhou He

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Influenza A Virus ◽

Influenza A ◽

H1n1 Virus ◽

Antiviral Agents ◽

Toll Like Receptor ◽

Virus Infections ◽

Toll Like Receptor 4 ◽

Inflammatory Cytokine Production

Influenza A virus infections can cause acute lung injury (ALI) in humans; thus, the identification of potent antiviral agents is urgently required. Herein, the effects of salidroside on influenza A virus-induced ALI were investigated in a murine model. BALB/c mice were intranasally inoculated with H1N1 virus and treated with salidroside. The results of this study show that salidroside treatment (30 and 60 mg/kg) significantly attenuated the H1N1 virus-induced histological alterations in the lung and inhibited inflammatory cytokine production. Salidroside also decreased the wet/dry ratio, viral titers, and Toll-like receptor 4 expression in the lungs. Therefore, salidroside may represent a potential therapeutic reagent for the treatment of influenza A virus-induced ALI.

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Bilobalide Ameliorates Sepsis Induced Acute Lung Injury by Inactivating Toll-Like Receptor 4/Myeloid Differentiation Factor 88/Nuclear Factor-Kappa B Pathway

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:277-282 ◽

2020 ◽

Vol 19 (3) ◽

pp. 277-282

Author(s):

Tian Liu ◽

Siyi Jiang ◽

Shengwei Jia ◽

Fuxiang Fan

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Nuclear Factor Kappa B ◽

Cecal Ligation ◽

Myeloid Differentiation ◽

Nuclear Factor ◽

Cecal Ligation And Puncture ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Myeloid Differentiation Factor

Acute lung injury refers to the injury of alveolar epithelial cells and pulmonary capillary endothelial cells caused by noncardiac factors. To better combat the disease, there is an urgent need to develop more effective drugs. Sepsis is a syndrome of systemic inflammation caused by infection, and the molecular mechanism by which sepsis induces acute lung injury has not been clearly determined. Bilobalide is a unique component of Ginkgo biloba. Although it has multiple biological functions, its role in sepsis induced acute lung injury needs further study. In this study, we found that bilobalide alleviated cecal ligation and puncture induced acute lung injury. Additionally, bilobalide regulated cecal ligation and puncture induced lung injury through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway. We therefore conclude that bilobalide may be a potential drug for the treatment of sepsis induced acute lung injury.

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The Effect of Experimental Diabetes on High Mobility Group Box 1 Protein Expression in Endotoxin-Induced Acute Lung Injury

Journal of Surgical Research ◽

10.1016/j.jss.2009.07.039 ◽

2011 ◽

Vol 168 (1) ◽

pp. 111-118 ◽

Cited By ~ 6

Author(s):

Satoshi Hagiwara ◽

Hideo Iwasaka ◽

Chihiro Shingu ◽

Shigekiyo Matumoto ◽

Akira Hasegawa ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Protein Expression ◽

Experimental Diabetes ◽

High Mobility ◽

High Mobility Group

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TNF-α Activates High-Mobility Group Box 1 - Toll-Like Receptor 4 Signaling Pathway in Human Aortic Endothelial Cells

Cellular Physiology and Biochemistry ◽

10.1159/000445570 ◽

2016 ◽

Vol 38 (6) ◽

pp. 2139-2151 ◽

Cited By ~ 16

Author(s):

Won Seok Yang ◽

Nam Jeong Han ◽

Jin Ju Kim ◽

Mee Jeong Lee ◽

Su-Kil Park

Keyword(s):

Signal Transduction ◽

Endothelial Cells ◽

High Mobility ◽

Neutralizing Antibody ◽

High Mobility Group ◽

Toll Like Receptor ◽

Toll Like Receptor 4 ◽

Aortic Endothelial Cells ◽

Tnf Α ◽

Human Aortic Endothelial Cells

Background/Aims: Toll-like receptor 4 (TLR4) interacts with endogenous substances as well as lipopolysaccharide. We explored whether TLR4 is implicated in tumor necrosis factor-α (TNF-α) signal transduction in human aortic endothelial cells. Methods: The pathway was evaluated by transfection of siRNAs, immunoprecipitation and Western blot analysis. Results: TNF-α activated spleen tyrosine kinase (Syk) within 10 min, which led to endothelin-1 (ET-1) production. TLR4 was also rapidly activated by TNF-α stimulation, as shown by recruitment of interleukin-1 receptor-associated kinase 1 to TLR4 and its adaptor molecule, myeloid differentiation factor 88 (MyD88). siRNA depletion of TLR4 markedly attenuated TNF-α-induced Syk activation and ET-1 production. TLR4 inhibitor (CLI-095), TLR4-neutralizing antibody and siRNA depletion of MyD88 also attenuated TNF-α-induced Syk activation. Syk was co-immunoprecipitated with TLR4, and TNF-α activated Syk bound to TLR4. High-mobility group box 1 (HMGB1) was rapidly released and associated with TLR4 after TNF-α stimulation with a peak at 5 min, which was prevented by N-acetylcysteine, an antioxidant. Glycyrrhizin (HMGB1 inhibitor), HMGB1-neutralizing antibody and siRNA depletion of HMGB1 all suppressed TNF-α-induced Syk activation and ET-1 production. Conclusion: Upon TNF-α stimulation, TLR4 is activated by HMGB1 that is immediately released after the generation of reactive oxygen species, and plays a crucial role in the signal transduction.

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